sábado, 28 de mayo de 2011
Pediatr Diabetes. 2011 May 12. doi: 10.1111/j.1399-5448.2011.00774.x. [Epub ahead of print]
The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants.
Hagopian WA, Erlich H, Lernmark A, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt R Jr, Blair A, Ilonen J, Krischer J, She J; the TEDDY Study Group.
Pacific Northwest Diabetes Research Institute, Seattle, WA, USA Roche Molecular Systems, Pleasanton, CA, USA Department of Clinical Sciences, Lund University, University Hospital UMAS, Malmö, Skåne, Sweden Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO, USA Diabetes Research Institute, Technische Universität München, Munich, Germany Department of Pediatrics, University of Turku, Turku, Finland DDEMD, NIDDK, Bethesda, MD, USA Newborn Screening Branch Division of Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, GA, USA Department of Clinical Microbiology, University of Kuopio, Kuopio, Finland Immunogenetics Laboratory, Department of Pediatrics, University of Turku, Turku Finland Department of Informatics and Biostatistics, Pediatrics Epidemiology Center, University of South Florida, Tampa, FL, USA Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta, GA, USA.
Hagopian WA, Erlich H, Lernmark Å, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt Jr R, Blair A, Ilonen J, Krischer J, She J, and the TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Aims: The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental factors influencing the development of type 1 diabetes (T1D) using intensive follow-up of children at elevated genetic risk. This study requires a cost-effective yet accurate screening strategy to identify the high-risk cohort. Methods: The TEDDY cohort was identified through newborn screening using human leukocyte antigen (HLA) class II genes based on criteria established with pre-TEDDY data. HLA typing was completed at six international centers using different genotyping methods that can achieve >98% accuracy. Results: TEDDY developed separate inclusion criteria for the general population (GP) and first-degree relatives (FDRs) of T1D patients. The FDR eligibility includes nine haplogenotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4b, DR4/1, DR4/13, DR4/9, and DR3/9) for broad HLA diversity, whereas the GP eligibility includes only the first four haplogenotypes with DRB1*0403 as an exclusion allele. TEDDY has screened 414 714 GP infants, of which 19 906 (4.8%) were eligible, whereas 1415 of the 6333 screened FDR infants (22.2%) were eligible. High-resolution confirmation testing of the eligible subjects indicated that the low-cost and low-resolution genotyping techniques employed at the screening centers yielded an accuracy of 99%. There were considerable variations in eligibility rates among the centers for GP (3.5-7.4%) and FDR (19-32%) subjects. The eligibility rates among US ethnic groups were 0.9, 1.3, 5.0, and 6.9% for Asians, Black, Caucasians, and Hispanics, respectively. Conclusions: Different low-cost and low-resolution genotyping methods are useful for the efficient and accurate identification of a high-risk cohort for follow-up based on the TEDDY HLA inclusion criteria (ClinicalTrials.gov NCT00279318).
© 2011 John Wiley & Sons A/S.
PMID:21564455[PubMed - as supplied by publisher]
The Environmental Determinants of Diabetes in the ... [Pediatr Diabetes. 2011] - PubMed result